ALK基因编码一种受体酪氨酸激酶(eceptor tyrosine kinase ,RTK),为跨膜蛋白,属于胰岛素受体超家族,在大脑发育与及特定的神经元中起重要作用。最初在间变性大细胞淋巴瘤(anaplastic large cell lymphoma, ALCL)发现ALK-NPM1融合蛋白,目前已在其它肿瘤中包括神经母细胞瘤和非小细胞肺癌,发现该基因出现突变、扩增或者重排,其中染色体重排最为常见,导致ALK与其他基因产生融合,包括ALK(2号染色体)/EML4(2号染色体),ALK / RANBP2(2号染色体),ALK /ATIC(2号染色体),ALK / TFG(3号染色体),ALK / NPM1(5号染色体),ALK / SQSTM1(5号染色体),ALK / KIF5B(10号染色体),ALK / CLTC(17号染色体),ALK / TPM4(19号染色体),和ALK / MSN(X染色体)。
氨基酸1151处插入t的alk融合变体发现于一种alk重排的肺腺癌中,该癌在对环唑替尼治疗作出反应后发展。在环唑天宁治疗前的肿瘤样本中没有突变。利用表达EML4-ALK的细胞系和1151t插入物对变体进行鉴定,发现该变体具有很高的环唑替尼抗性,其他研究表明该变体对下一代抑制剂阿来替尼具有抗性,而对工具化合物TAE684的抗性则表明该变体对下一代ALK抑制剂铈替尼具有潜在的抗性,后者是D。源自TAE684。其他实验表明热休克蛋白90抑制剂的治疗潜力,因为已经观察到EML4-ALK T1151 Tins对17-AAG的敏感性。
The ALK fusion variant with insertion of T at amino acid 1151 was found in an ALK rearranged lung adenocarcinoma which had progressed after responding to crizotinib treatment. The mutation was absent in tumor sample taken before crizotinib treatment. Characterization of the variant using cell lines expressing EML4-ALK with 1151 T insert found the variant to be highly crizotinib resistant, and other work demonstrated resistance to next generation inhibitor alectinib, while resistance to tool compound TAE684 indicates potential resistance to the next generation ALK inhibitor ceritinib which is derived from TAE684. Other experiments suggest theraputic potential for HSP90 inhibitors, as EML4-ALK T1151 Tins sensitivity to 17-AAG has been observed.
| Chr. | Start | Stop | Ref. s | Var. Bases |
| 2 | 29445271 | 29445272 | CGT | |
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| ENST00000389048.3 | ||||